Tuesday, April 29, 2014

Fish and Krill Oil Both "Work" But Their Effects on Your Genes Are Far From Identical. Krill May Bet Better For the Obese, While Fish Acts as a "Fat Modulator" in Lean Folks

If krill oil is not fish oil 2.0 what is it good or even bad for, then?
For SuppVersity Veterans, it's no news that phospholipid-bound omega-3 fatty acids (as in krill oil) have a superior bioavailability compared to triglyceride bound ones (as in fish oil) - you've read about that in in June 2012 in an article titled "Phospholipid or Triglyceride" (go back and read it!). This and the fact that the latest paper from the Karolinska Institutet, in Sweden, the University of Bergen and the Haukeland University Hospital in Bergen, Norway, is yet another rodent study had me hesitate before I picked up Roy Nelson's suggestion to discuss the surprisingly differential effects of fish and krill oil on the tissue concentration and lipid metabolism of mice, not men.

As I previously mentioned, the low rate of incorporation of triglyceride-bound omega-3 fatty acids into the tissue of the Male C57BL/6J mice, which were kept on a high fat diet that contained 24% (wt/wt) fat (21.3% lard and 2.3% soy oil), or, alternatively, the same HF diet supplemented with FO (15.7% lard, 2.3% soy oil and 5.8% FO) or KO (15.6% lard, 2.3% soy oil and 5.7% KO) for 6 weeks, is eventually not surprising.
You can learn more about omega-3 & co at the SuppVersity

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Eventually, you can think of the difference between phospholipid bound (P) and triglyceride bound (T) fatty acids with respect to their chances of being incorporated into your cells as bricks (P) and menirs (T). Obviously, the former can be used right away, to build a new home. The latter, on the other hand, have to be processed, before they can become part of a building - or, if we leave our analogy, your cells. If you have enough "stones" aka omega-3s - and the 5.8% fish oil in the diet obviously were more than enough - you will still end up at similar serum levels (obviously it's not exactly feasible to consume ~6% of your diet, i.e. at least 120kcal = 13g of fish oil, everyday; therefore bioavailability still is a clear advantage for krill oil).

Popping more than 10g+ of fish oil a day is madness. Making the right fish choices and eating those fish twice a week, on the other hand, is smart!
So if that's not really news, what makes the study news-worthy, then? Well, that's actually a good question, which takes me right to observation #2: While the allegedly bad arachidonic acid, the long-chain omega-6 counterpart to the celebrated omega-3 stars, EPA & DHA, of which the SU.FOL.OM3 Trial recently taught you that it's good for your brain (go back), was reduced with both oils, the krill oil, which is per definition less omega-3 dense (there are more non-omega-3 fatty acids in it) had decreased the levels of this (imho falsely vilified) "inflammatory" fatty acid and its elongation/desaturation products in plasma and liver to a significantly greater extent.

In conjunction with its effects on the expression of genes involved in the early steps of isoprenoid/cholesterol and lipid synthesis, the ability to "clear" the pro-inflammatory arachidonic acid from your blood makes krill oil the perfect choice for people who suffer from chronic inflammation.
None of the 20 agents in the list of anti-obesity agents is going to do the work for you, but they could help you "conserve" the results, keep you lean on a bulk and/or avoid the hazardous Yoyo effect when you go off a die.
Krill oil favors the storage of glucose as fat: There is another effect that makes krill oil particularly interesting for the average overweight pro-diabetic. As a recent study from the Iwate University reveals (Yamada. 2014), 8-HEPE and 9-HEPE two metabolites of the well-known omega-3 fatty acid EPA that are present in high amounts in krill oil are potent PPAR-alpha, -gamma and delta activator. With PPAR-gamma being the "fat storage" switch (learn more) this is fortunate for the (non-)obese diabetic for whom it will help him clear the glucose from the blood and store it in the adipose organ. For the lean athlete on the other hand, the 20 PPAR-gamma inhibitors, I listed in a previous article with the telling title " Fighting to Stay Lean? These 20+ Anti-Obesity Agents Have the Potential to Inhibit Fat Gain Right at the Cellular Level" would certainly be a better choice.
For fish oil, things look (not generally but) slightly different. While fish oil will also have an impact on arachidonic acid and cholesterol synthesis, the scientists found that its effects on the liver and the downstream effects on the levels of triglycerides,  phospholipids and the very low density lipoprotein (VLDL) in the blood, as well as their accumulation in the liver is significantly more pronounced for fish vs. krill oil.

It's not all gold that glitters like fish oil, but "Krill Red" ain't necessarily better either

If you look at the data in Figure 1, you will also realize that fish oil had visibly (carnitine palmitoyl transferase 1 CPT1, ACOX), but not significantly more potent effects on the activity of fat burning enzymes in the liver. In view of the fact that the net results in form of body weight gain where identical, it's yet not just statistically, but probably also practically irrelevant.
Warning: Fish oil can clog your liver, as well and the increase in fatty acid synthesis in the liver (FAS) you see in Figure 1 could actually explain the observations I report in "Too Much of a Good(?) Thing: When Fish Oil Starts Clogging Your Arteries and Fattening Up Your Liver." | read more.
Although, if you think of a high triglyceride scenario, the use of fish oil appears to be a better choice to reduce the amount of the "carbohydrates" among the fatty acids (trigs will usually rise in response to problems w/ glucose metabolism and drop rock bottom in most people who stop eating carbs).
Figure 1: Rel. changes (% of HF diet) in liver fatty acid metabolism (left) and body weight development (right) of the mice over the study period (calculated base on Tillander. 2014)
This "advantage" is in line with the differential expression of  genes involved in fatty acid modulation and transport in the intestine. Only the fish oil, yet not the krill oil diet had significant effects on these PPAR╬▒ driven genes, of which we believe that they are responsible for the immediate benefits of fish oil supplementation on postprandial (after the meal) plasma lipid levels and ╬▓-oxidation (less fats are absorbed, more are burnt right away - the importance of this effect is yet, as Tillander et al. point out "likely to be small".
Make up your mind: I would not say that there is yet a "right or wrong" with respect to the ingestion of fish oil and other omega-3 fatty acids in supplemental form. You know my scepticism, but it's obviously up to you to make up your mind.

If you browse previous SuppVersity articles, you will realize that there are actually arguments for both supplementing with (sane!) amounts of fish oil and touching none of the fishy pills, at all.
Bottom line: Practically speaking, its superior bioavailability, as well as its potent effects the levels of arachidonic acid and its metabolites in your blood make krill oil the better choice for people with a high baseline inflammation level. For them, the reduction in arachidonic acid takes away the "fuel" to the fire that's burning the cell lines of their arteries and organs and that's - unquestionably - a good thing.

The increased propensity for fatty acid storage in the adipose organ (not in the liver!) that was observed by Yamada et al., as well as the higher expression of "pro-oxidative" genes in the liver of which you would expect that it goes hand in hand with an increase in fatty acid oxidation appears to make fish oil, the better choice for the healthier individual. This does yet not mean that I've changed my mind: I still don't think that taking more than max. 2g of fish oil per day is beneficial for an individual who trains, eats clean (=no processed foods) and consumes fatty fish at least once a week. For him, or her, I actually wouldn't suggest taking any fish oil.
  • Tillander et al. "Fish oil and krill oil supplementations differentially regulate lipid catabolic and synthetic pathways in mice". Nutrition & Metabolism 2014, 11:20 doi:10.1186/1743-7075-11-20
  • Yamada, Hidetoshi, et al. "Hydroxyeicosapentaenoic acids from the Pacific krill show high ligand activities for PPARs." Journal of lipid research 55.5 (2014): 895-904.